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02-06-2013 | Genetics | Article

Primary NSCLC shares mutations with metastases

Abstract

Free abstract

medwireNews: Scientists have found a high level of concordance in the genetic mutations of pairs of primary non-small-cell lung cancer (NSCLC) and metachronous or synchronous metastases.

"Our data indicate that archived primary material could be a suitable specimen for clinical decision on development of metastatic disease," Jean-Charles Soria (INSERM U981, Institut Gustave Roussy, Villejuif, France) and co-workers write in the Journal of Clinical Oncology.

"If confirmed in a larger series, such results do not support the routine need for a new biopsy on first recurrence solely for these purposes, since variability in recurrent alterations status is low."

Genomic libraries were created for matched specimens of primary tumor and metastases taken from 15 patients, covering 3230 exons in 182 cancer-related genes and 37 introns in 14 other genes frequently rearranged in cancer.

This revealed 311 genomic alterations in the samples, the majority of which were nonrecurrent "passenger" mutations unlikely to have any impact on tumor development, report

However, 63 previously known recurrent alterations were detected in the primary (n=32) and metastatic (n=31) samples. TP53 was the most commonly affected gene, altered in both samples of 12 patients, with one of these patients also having a EGFR alteration in both their primary and metastatic sample.

Other genes affected in the primary tumor, metastases, or both samples included KRAS in four patients, PIK3CA in three patients, and STK11 in three patients. Ten patients had between two and four known mutations in their tumors.

Overall, the concordance rate for the known alterations found in primary tumors and matched metastases was 94%, compared with just 63% for passenger mutations.

Nevertheless, Soria et al caution that "the need for a new biopsy of a metastatic lesion may be crucial in order to understand acquired resistance, and future studies should focus on the question of putative selection pressure during the disease course of each patient."

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Lynda Williams, Senior medwireNews Reporter